Researchers Find Defects In Adult Stem Cell Niche May Cause Breast Cancer

The research, published in the October2005 issue of Tissue and Cell, is the first to examine the highlyspecialized microenvironment, termed the stem cell niche, whichsurrounds adult stem cells, and its role in breast cancer development.These niches are key regulators of stem cell activity in mammarytissue, and defects that develop in these groups of cells can give riseto breast cancer.

“This study helps us understand adult stemcells differently than we previously did. Particularly, when lookingfor the causes of breast cancer, we must take into account the stemcell as well as the environment that surrounds it,” said RobertDickson, Ph.D., co-author of the paper and co-director of the breastcancer program at the Lombardi Comprehensive Cancer Center.

Thestudy used genetically engineered mice as models of ductal or lobularbreast cancer that is caused by overproduction of certain proteins.These proteins (c-Myc and TGF-alpha) exist naturally in the body, butwhen produced in excess in mammary tissue cells, breast cancer candevelop.

Gloria Chepko, Ph.D., a postdoctoral fellow and thepaper’s lead author, built on previous research results thatdemonstrated the existence of five different types of cells in normalbreast tissue. Two of the cell types are stem cell-like and give riseto the other three. For the present study, she devised a method toidentify all the cell types at low magnification, allowing more cellsto be counted. This method revealed not only that each cell populationhas a different size in normal breast tissue, but also that thedifferent cells are arranged in particular relationships to each other.The arrangements form repeating units called stem cell niches andprovide nest-like microenvironments that house the adult stem cells andtheir immediate daughter cells.

In the mice that expressedexcess amounts of either of the cancer-producing proteins, the size ofthe cell populations were significantly changed relative to each other.The order of the cell arrangements was disrupted in the stem cellniches of mice with breast cancer. These results provided the firstevidence that each cell population may play a different role in thedevelopment of breast cancer and that the environment in which a cellgrows can influence its chance of becoming cancerous.

“Theresults also show how complicated cancer is as a disease. Although it’snot something that will be solved easily or quickly, our study revealsimportant information on the genesis of breast cancer in the body,”said Chepko.

The study was funded in part by a grant from theNational Institutes of Health and by a grant from the Department ofDefense, both of which received funds from sales of the U.S. PostalService breast cancer stamp. Co-authors include Rebecca Slack, M.S.,Deborah Carbott, Sonya Khan and Lynley Steadman from GeorgetownUniversity.

The Lombardi Comprehensive Cancer Center, part ofGeorgetown University Medical Center and Georgetown UniversityHospital, seeks to improve the diagnosis, treatment and prevention ofcancer through innovative basic and clinical research, patient care,community education and outreach, and the training of cancerspecialists of the future. Lombardi is one of only 39 comprehensivecancer centers in the nation, as designated by the National CancerInstitute, and the only one in the Washington DC area. For moreinformation, go to http://lombardi.georgetown.edu/